Weak hydrogen bonds in fluorine substituted biomolecules

Fluorine substitution in molecules is a common practice in bio-organic chemistry in order to modulate physicochemical properties and biological activity of molecules and in the case of adrenergic neurotransmitters cases the selectivity of the molecules is dramatically altered depending on the site of fluorination.(1) 4-fluoro and 2-fluoro-2-phenylethylamine (analogs of the prototype 2-phenylethylamine) were studied by rotational spectroscopy and ab initio calculations with the scope of obtaining information on the effects of fluorination on the conformational energy landscape. The conformational space is dominated by low energy gauche conformations stabilized by weak hydrogen bonds and higher energy anti conformations. The order of stability of the conformers is altered with respect to the prototype molecule, and these observations are rationalized in terms of the effect of fluorine on the charge distribution of the  cloud. (1) C. Pooput, E. Rosemond, J. Karpiak, F. Deflorian, S. Vilar, S. Costanzi, J. Wess and K. L. Kirk, Bioorg. & Med Chem., 2009, 17, 7987